On October 16, 2019 NOXXON Pharma N.V. (Euronext Growth Paris: ALNOX), a biotechnology company focused on improving cancer treatments by targeting the tumor microenvironment (TME), reported the enrollment and first treatment of a patient with newly diagnosed brain cancer in a phase 1/2 clinical trial (Press release, NOXXON, OCT 16, 2019, View Source [SID1234542276]). The study investigates a combined therapy of increasing doses of the CXCL12 inhibitor, NOX-A12, and external-beam radiotherapy. Within this study, NOX-A12 administration in planned for up to six months. The anticipated mode of action of NOX-A12 is the inhibition of the unwanted influx of bone marrow-derived "repair cells" to the tumor following radiotherapy-induced breakdown of the vasculature in the tumor. These "repair cells" act by replacing the tumor’s blood vessels that were destroyed by the irradiation, which ultimately results in disease recurrence.

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The study is designed to deliver safety and first efficacy data to support the definition of a Recommended Phase 2 Dose (RP2D) for this new treatment approach. In addition, the noninvasive assessment of the changes in tumor vascularization is expected to confirm the predicted mechanism of action for the combination of NOX-A12 and radiotherapy.

"The trial represents a new option for very difficult-to-treat patients. The candidate drug should block the influx of two distinct types of cells that the damaged brain tumor tries to recruit to help repair itself and survive. A plethora of pre-clinical studies as well as a recent clinical trial at Stanford yielded promising results with interventions targeting the CXCL12 pathway. We learnt some lessons from these data, and we are very optimistic that blocking both cell types for a longer duration will be even more effective," commented Dr. Frank Giordano, Interim Director of the Department of Radiation Oncology at the University Medical Center Mannheim.

"Based on promising preclinical data in rat and mouse models, we are excited to evaluate NOX-A12 in this indication. It is a unique and promising approach with the potential to effectively treat brain cancer patients for whom there are currently no optimal therapies. The demand from the clinical community to test this combination has been very strong and we are pleased that the dosing of patients has been initiated. We expect data from the first cohort of patients to be available in mid-2020," added Dr. Jarl Ulf Jungnelius, Chief Medical Officer of NOXXON.

The trial is being conducted at three hospitals in Germany. Up to three escalating doses of NOX-A12 will be administered in combination with standard radiotherapy as a first line treatment to newly diagnosed patients with brain tumors who would not benefit from the current standard of care of chemotherapy and whose tumors cannot be fully resected by surgery. The main objective of the study is to assess the safety and tolerability of this combination. Secondary endpoints include activity of the therapy, assessed through the monitoring of tumor vascularization by MRI scans, progression-free survival, overall survival and rates of response.

On October 15, 2019 SQZ Biotechnologies (SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas, reported the expansion of its collaboration with Roche (SIX: RO, ROG;OTCQX: RHHBY) in cellular therapy (Press release, SQZ Biotech, OCT 15, 2019, View Source [SID1234553406]). The expanded partnership furthers the synergistic combination of SQZ’s innovation and expertise in cell therapy with Roche’s cancer immunotherapy expertise. Under the terms, SQZ and Roche will jointly develop and commercialize certain products based on antigen presenting cells (APCs) created by the SQZ platform for the treatment of oncology indications.

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"We believe that this new expanded collaboration accelerates our ability to bring a broad range of impactful oncology products to market," said Armon Sharei, PhD, founder and Chief Executive Officer of SQZ. "We have an ambitious scientific and clinical vision to create transformative cell therapies at SQZ, and we believe our alliance with Roche will yield novel therapeutics for cancer patients."

Under the collaboration, SQZ may receive up to $125 million in upfront payment and near-term milestones. SQZ could earn up to $250 million in clinical, regulatory and sales milestones per product that emerges from the collaboration. In addition, SQZ may receive development milestone payments of over $1 billion. Within the collaboration, SQZ and Roche could share commercial rights for certain approved products.

SQZ APCs leverage native immune functions to spark target-specific killer (CD8) T cell responses in vivo. Through effective presentation of antigens on MHC-I, SQZ APCs can directly stimulate CD8 T cell activity and potentially drive powerful anti-tumor effects that address antigens inaccessible by other adoptive cell-based cancer immune therapy strategies. In addition to their broad targeting potential, the SQZ APC engineering and manufacturing process requires no cellular expansion or genetic modification by viruses or editing agents, thereby dramatically improving the anticipated safety profile, cutting production time, and cost.

The companies will expand the 2015 Roche collaboration to jointly develop therapeutics derived from peripheral blood mononuclear cells (PBMCs).

Howard Bernstein, MD, PhD, Chief Scientific Officer of SQZ, commented "By creating a PBMC APC platform, this collaboration allows for a SQZ APC product engine that could potentially generate products with more potent immunologic responses through a simplified, more efficient manufacturing process."

About SQZ APCs
Antigen presenting cells (APCs), are cells that present antigen on their surface through major histocompatibility complexes (MHCs). APCs are primarily responsible for activating endogenous T cell responses and play a critical role in physiological responses against viruses and tumors. SQZ technology can uniquely access APC biology to engineer effective loading of their MHCs with tumor antigens. When SQZ APCs are injected into an animal, their MHC presented antigens induce powerful, specific CD8 T cell (i.e. killer T cell) responses against the antigen of interest. These CD8 T cells can subsequently drive a strong killing effect against any cell expressing the target antigen. SQZ APCs thus provide a promising platform to drive patient CD8 T cell responses against any tumor target of interest for implementation in a wide range of oncology indications.

On October 15, 2019, Seelos Corporation ("STI"), a wholly-owned subsidiary of Seelos Therapeutics, Inc. ("Seelos"), and Phoenixus AG f/k/a Vyera Pharmaceuticals AG ("Vyera"), reported that it entered into an amendment (the "Amendment") to the Asset Purchase Agreement by and between STI and Vyera, dated March 6, 2018 (the "Initial Agreement"), as amended by a first amendment thereto entered into on May 18, 2018 (the "First Amendment"), and a second amendment thereto entered into on December 31, 2018 (the "Second Amendment" and the Initial Agreement, as amended by the First Amendment and the Second Amendment, the "Purchase Agreement") (Filing, 8-K, Apricus Biosciences, OCT 15, 2019, View Source [SID1234542378]). Pursuant to the Initial Purchase Agreement, STI acquired the assets (the "Vyera Assets") and liabilities (the "Vyera Assumed Liabilities") of Vyera related to a product candidate currently referred to as SLS-002 (intranasal ketamine). Pursuant to the Purchase Agreement, STI agreed that if it received regulatory approval to commence a Phase III clinical trial for SLS-002 and no third party had alleged any claim of conflict, infringement, invalidity or other violation of any rights of others with regard to the Vyera Assets, STI would commence a Phase III clinical trial for SLS-002 by June 30, 2020 (the "Phase III Obligation"), and if STI failed to do so, the Purchase Agreement would terminate immediately and become null and void and all of the Vyera Assets and the Vyera Assumed Liabilities would automatically be returned to Vyera. The Purchase Agreement further provided that as partial consideration for the Vyera Assets, STI agreed to make to Vyera certain one-time, non-refundable milestone payments, including a $3.5 million cash payment upon dosing of the first patient in a Phase III clinical trial for SLS-002 (the "Dosing Milestone").

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Pursuant to the Amendment, STI remains obligated to use its commercially reasonable efforts to seek regulatory approval in the United States for and commercialize SLS-002. However, the Amendment eliminates the Phase III Obligation. In addition, in replacement of STI’s obligation to pay the Dosing Milestone, STI agreed pursuant to the Amendment to (i) issue Vyera in January 2020 that number of registered shares of Seelos common stock equal to $2,250,000 divided by a 30-day volume weighted average price of the common stock calculated prior to such issuance date and (ii) make cash payments to Vyera in the amounts of $750,000, $750,000, $1 million and $1 million in October 2019, early January 2020, early April 2020 and early July 2020, respectively (each, a "Payment Obligation"). In event STI fails to timely meet a Payment Obligation (subject to a cure period), Vyera has the right to require that all of the Vyera Assets and the Vyera Assumed Liabilities be returned by STI to Vyera.

On October 15, 2019, Aclaris Therapeutics, Inc. (the "Company") and Rigel Pharmaceuticals, Inc. ("Rigel") reported that it entered into a First Amendment (the "First Amendment") to the License and Collaboration Agreement, originally dated as of August 27, 2015 (the "Original Agreement") (Filing, 8-K, Aclaris Therapeutics, OCT 15, 2019, View Source [SID1234542327]).

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Pursuant to the First Amendment, the Company and Rigel agreed to eliminate certain of the development milestones and Rigel released the Company from any obligation to pay a milestone payment for such milestones. The Company also agreed to pay Rigel an amendment fee of $1.5 million to be paid in three equal tranches of $500,000 in January 2020, April 2020 and July 2020. In addition, the parties modified certain other development milestones, and the Company agreed to increase the potential payments payable upon the achievement of such milestones from $10.0 million to $10.5 million in the aggregate. The First Amendment also provides that the Company’s obligation to use commercially reasonable efforts to develop, seek regulatory approval and commercialize at least one product would be deemed satisfied by the Company using commercially reasonable efforts to find a third party to use commercially reasonable efforts to develop, seek regulatory approval and commercialize at least one product.

Except as modified by the First Amendment, all terms and conditions of the Original Agreement remain in full force and effect.

On October 15, 2019 Cyteir Therapeutics, a leader in the discovery and development of next-generation synthetic lethal therapies for cancer, reported the close of an additional $40.2 million in the company’s Series B financing, for a total of $75.2 million in this financing (Press release, Cyteir Therapeutics, OCT 15, 2019, View Source [SID1234542288]). The additional funding will be used to expand the clinical investigation of Cyteir’s first-in-class RAD51 inhibitor and lead compound, CYT-0851, and to identify new targets using the company’s novel gain-of-function synthetic lethality screening platform.

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Novo Holdings led the round, joined by existing investors Venrock, DROIA Oncology Ventures, Osage University Partners (OUP), Lightstone Ventures and Celgene Corporation. As part of this closing, Karen Hong, Ph.D., of Novo Ventures, which provides consulting services to Novo Holdings, will join the Cyteir Board.

"The continued support for Cyteir from highly knowledgeable investors reflects the growing excitement around our novel application of synthetic lethality," said Markus Renschler, M.D., Cyteir president and CEO. "This financing will support the recently launched first-in-human phase 1/2 study of CYT-0851 while simultaneously allowing us to continue investigating our synthetic lethality platform to find new targets that inhibit DNA damage repair. We believe this approach could lead to valuable new treatment options for cancer patients."

Cyteir’s platform is based on the discovery of a relationship between DNA-damaging enzymes known as cytidine deaminases, and RAD51, a protein that is essential for the repair of DNA breaks. These enzymes are non-damaging in healthy tissues, but gain hyperactive function in a wide range of cancers and cause elevated DNA damage. Cyteir is developing selective small-molecule inhibitors of RAD51 to reduce the ability of cancer cells to self-repair through homologous recombination. This causes the cancer cells to become overwhelmed by accumulated DNA damage and undergo cell death – resulting in the therapeutic effect known as "synthetic lethality."

In preclinical experiments, CYT-0851 demonstrated synergy with PARP inhibitors, consistent with its DNA damage-repair pathway inhibitory activity. These results suggest CYT-0851 has the potential to overcome PARP inhibitor resistance.

Researchers at Sarah Cannon Research Institute in Nashville, Tenn., recently dosed the first patient in a Phase 1/2 study of CYT-0851. This study will enroll up to 200 patients with B-cell malignancies and solid tumors.

"We are pleased to be part of this study, which will help define the potential of an entirely new class of targeted cancer therapy," said Johanna Bendell, M.D., chief development officer at Sarah Cannon Research Institute and the study’s lead investigator. "Pre-clinical evaluations of CYT-0851 have been very encouraging, and we look forward to seeing how this compound impacts patients in this trial."

In March 2019, Cyteir presented pre-clinical data at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting that validated the mechanism of action underlying the company’s synthetic lethal platform and confirmed that CYT-0851 is a potent inhibitor of RAD51-mediated homologous recombination with the potential to target multiple cancers that have high levels of cytidine deaminase-related DNA damage. The data indicated that CYT-0851 could potentially be clinically active as a monotherapy against B-cell lymphomas and multiple solid tumors, including pancreatic cancer.

About the CYT-0851 Phase 1/2 Trial

CYT-0851-01 is a phase 1/2 study of CYT-0851 in patients with relapsed, refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, multiple myeloma, or advanced breast cancer, ovarian cancer, head and neck cancer, soft tissue sarcoma, and pancreatic cancer. The study will be conducted at leading research institutions in the United States. An initial dose-escalation phase will establish the safety and tolerability of CYT-0851 and identify the recommended phase 2 dose. This will be followed by an expansion phase to evaluate response rates among each of six disease cohorts. Cyteir is also developing a companion diagnostic assay to identify patients with tumors that overexpress certain cytidine deaminases that may make them more susceptible to RAD51 inhibition.

About CYT-0851

CYT-0851 is an experimental, oral, selective inhibitor of RAD51, a protein involved in homologous recombination. Cancer cells that overexpress certain DNA-damaging cytidine deaminases rely on RAD51 to repair DNA damage. In preclinical models, inhibition of RAD51 with CYT-0851 induces cell death in cytidine deaminase overexpressing cell lines and reduces proliferation.